The Hypertension Specialized Center of Research at Boston University will provide a broad-based and multidisciplinary approach to the study of cellular and molecular mechanisms involved in the pathogenesis and complications of hypertension. A major goal of the program will be to determine the role of sodium, humoral factors, and their interrelationships in the etiology of hypertension. These studies will include investigation of: a) the regulation of sodium transport in cultured rental medullary epithelial cells and arterial smooth muscle cells from normotensive and hypertensive rats; b) the contribution of 19-nor-deoxycorticosterone to elevated blood pressure in human and experimental forms of hypertension; c) the role of the sodium pump and the expression and regulation of the isoforms of Na, K- ATPase in heart, artery, and other tissues of hypertensive animal models; d) genetic studies in hypertensive patients with a strong family history of the disease to determine the presence of a restriction fragment length polymorphism of the alpha-1 isoform of Na, K-ATPase demonstrated recently by us in both the Dahl salt-sensitive and spontaneously hypertensive strains; e) the cloning and characterization of angiotensin II receptors, their tissue regulation, and their potential role in hypertension; f) the role of bradykinin and its interaction with other vaso-active systems in cardiovascular hemodynamics and hypertension utilizing a new, relatively specific inhibitor of bradykinin prepared in our laboratory; g) the kallikrein-kinin system in intact arteries and cultured vascular cells, and the expression of components of this system, their regulation, and response to hypertension; and h) the importance of V1 and V2 classes of vasopressin receptors in human and experimental hypertension and heart failure using specific inhibitors of these receptors which have been prepared in our laboratory. Another major emphasis of the studies also will be on the mechanisms by which hypertension and hypercholesterolemia induce arterial injury and atherosclerosis. The expression of selected growth factors and of connective tissue components will be examined to determine the autocrine and paracrine interactions involved in the development of vascular disease. The cause of functional abnormalities in arterial rings induced by hypertension and hypercholesterolemia will be assessed and their relationship to changes in G-proteins and growth factors will be determined. Furthermore, the effects of cardiac hypertrophy on cardiac structure and function and on the response of isolated hearts to potentially injurious stimuli will be studied. The Hypertension SCOR should provide important new knowledge on the causes and consequences of hypertension and should lead to new approaches on its prevention and treatment.